1. We have completed our second year of acquisition of normative data for various aspects of auditory and vestibular function. This data will serve as reference ranges of normal performance by which test results can be interpreted as normal or abnormal, and will be used as control data for the purpose of comparison to data obtained in various patient groups in our collaborative research. We also plan to examine the effects of various methodologies, stimulus characteristics, test equipment, test paradigms, and the influence of non-pathologic subject characteristics (e.g. age, gender) on normal function, and to evaluate intra-subject variability on auditory and vestibular measures. To date we have focused on the development of normative data for tests evaluating otolith function and have made two presentations at professional society meetings on this topic (Zalewski et al. 2014). 2. In collaboration with Drs. Griffith and Friedman (NIDCD), Dr. Moore (Cincinnati Childrens Hospital), and Dr. Zobay (Institute for Hearing Research, UK) we are analyzing data from a series of non-speech tests developed to evaluate sensory/temporal aspects of auditory processing. These tests were administered to twins attending an annual twins festival in an effort to determine heritability of auditory processing skills. We have previously identified heritability of speech-based auditory processing skills and this work extends our research to evaluation of non-speech based skills. We have two manuscripts in preparation. 3. In collaboration with the Molecular Biology and Genetics section (Dr Griffith), the Audiology Unit performs auditory and vestibular phenotypic assessments of individuals with hearing loss and enlarged vestibular aqueducts (EVA), as well as their siblings and parents. Over 90 probands and their families have now been ascertained. The audiology unit continues to evaluate details of the vestibular and auditory phenotype to search for features that predict genotype, clinical prognosis, or clinical diagnosis. We contributed to two manuscripts since that last annual report (Chattaraj et al. Sept 2013, and Chien et al, submitted). 4. In collaboration with Drs. Friedman and Griffith of the NIDCD and Dr. Zein (NEI), the Audiology Unit continues to evaluate auditory and balance function in persons with Usher Syndrome. We are interested in postural balance skills and their relationship to vestibular and visual function, type of Usher syndrome, and the progression of these skills over time. We have contributed to one manuscript in 2014 (Zein et al., in submission) and presented a poster at the NIH Research Festival in October 2013 (Wafa et al.). 5. In collaboration with Dr. Drayna (NIDCD), we have prepared an auditory test protocol to investigate a group of participants with stuttering. 6. In collaboration with Dr. Cunningham (NIDCD), we initiated development of a test protocol to document the effectiveness of an otoprotective methodology for patients receiving ototoxic medications. 7. In collaboration with Dr. Forbes D. Porter (NICHD), we participated in a phase 1 trial of Hydroxypropyl beta cyclodextrin for treatment of Neimann Pick Type C (NPC) disease. Our roles include monitoring and grading of auditory function, participation on the safety committee, and participation in the NIH/NCATS NPC Ototoxicity Meeting and other discussions regarding this treatment. Additionally, we published two papers on the auditory phenotype of NPC, one in the mouse model (King et al., 2014) and one in humans (King et al., 2014). 8. In collaboration with Dr. Raphaela Goldbach-Mansky (NIAMS) we continued evaluation of auditory manifestations of neonatal onset multi-system inflammatory disorder (NOMID), familial cold auto-inflammatory syndrome, and Muckle-Wells syndrome and the effectiveness of several drug therapies. This work resulted in one publication in the past year (Sibley et al., 2014). 9. In collaboration with Dr. Brian Brooks (NEI) we evaluated auditory function in persons with coloboma. This work has contributed to one manuscript (Huynh et al., Dec 2013). I0. In collaboration with Dr. Stephen Holland, (NIAID) we collected research data and contributed to manuscripts evaluating the auditory phenotypes of GATA2 (Spinner et al., 2014) and the auditory and vestibular phenotypes of GATA3 (Chien et al., 2014). 11. In collaboration with Drs. Kenneth Olivier and Stephen Holland (NIAID) we conducted auditory evaluations and contributed to a manuscript on the use of inhaled amikacin for refractory pulmonary nontuberculosis mycobacterial disease (Olivier et al, 2014). 13. In collaboration with Dr. Meral Gunay-Aygun (NHGRI) we evaluated auditory function, including evoked potentials, in patients with Alstrom syndrome and presented a poster on this topic at a professional society meeting (Brewer et al. 2014). 14. In collaboration with Dr. Charles Venditti (NHGRI) we evaluated and analyzed the natural history of auditory function in patients with methylmelonic acidemia. This resulted in a poster presentation (Nast et al., 2014) at a professional society meeting. 15. In collaboration with investigators from other NIH institutes, we are evaluating hearing, electrophysiologic auditory function, and central auditory processing manifestations in persons oculocutaneous albinism (Dr. Adams, NHGRI), neurofibromatosis type I (Dr. Widemann, NCI), Congenital Disorders of Glycosylation (Dr. Gahl, NHGRI), gangliosidosis types 1 and 2 (Dr. Tifft, NHGRI). We are interested in the auditory phenotype, including processing of dichotic and other complex sounds, and relationships to other aspects of the disease/disorder and genotype. We presented a poster at professional society meeting on the topic of GM1 (King et al. 2014). 16. In collaboration with Dr. Heiss (NINDS), we are evaluating hearing, electrophysiologic auditory function, vestibular function, and postural balance in persons with neurofibromatosis type 2. We are interested in sensitivity of these assessments in early detection and monitoring of vestibular schwannomas. This work resulted in a publication during 2014 (Holliday et al.). 17. We continue to evaluate natural history of auditory function in persons with Fanconi anemia and other inherited bone marrow failure syndromes (IBMFS) (Dr. Alter, NCI), McCune-Albright syndrome and polyostotic fibrous dysplasia (Dr. M. Collins, NIDCR), von Hippel-Lindau disease (Lonser, NINDS), Smith-Magenis syndrome (Ms. Smith, NHGRI), WHIMS (Dr. McDermott, NIAID), osteogenesis imperfecta (Dr. Marini, NICHD), Y-Chromosome variants (Dr. Muenke, NHGRI), xeroderma pigmentosum and trichothiodystrophy (Drs. Kraemer and Digiovanna) and the Undiagnosed Diseases Program (Dr. Gahl, NHGRI). We are interested in the auditory phenotype, natural history of hearing, and relationships to other aspects of disease/disorder and genotype. We wrote a newsletter article (Temporal Bone Registry Newsletter) on the otopathology of xeroderma pigmentosum published in Fall 2013. 18. In collaboration with investigators from other NIH institutes, we are evaluating hearing and vestibular function in persons with exposure to breacher explosions (Drs. Wasserman and LoPresti, NINDS). We are interested in the effects of repeated exposures on the auditory and vestibular systems. 19. In collaboration with investigators from other NIH institutes, we continue to implement and analyze studies of the auditory and/or vestibular system of persons participating in clinical procedures or therapies in which these systems may be at risk. These include aminoglycosides for mycobacterium infections (Drs. Holland and Olivier), antineoplastic compounds (Drs. Gramsa and Hassan, NCI), radiation therapy for brain tumors (Dr. Warren), and transcranial magnetic stimulation (Drs. Hallett and Damiano, NINDS).